Pyridine derivatives



iii 2975559116 UflitCt 1 2,758,116 PYRIDINE DERIVATIVES Frederick Y. Wiselogle, Kathryn A. Losee, and Jack Bernstein, New Brunswick, N. J., assignors to Olin Mathieson Chemical Corporation, New York, N. Y., a corporation of Virginia No Drawing. Application March 8, 1956, Serial No. 570,215 9 Claims. (Cl. 260-2943) This invention relates to new chemical compounds and more particularly to mixed anhydrides of l-hydroxy-Z- pyridinethiones and fatty acids.

The preferred compounds of this invention are those of the general formula wherein R is a hydrocarbon aliphatic radical, R is hydrogen, lower alkyl, lower alkoxy or halogen, and n is positive integer no higher than four (preferably one). Suitable values for R include: alkyl, such as lower alkyl (e. g., methyl, ethyl, propyl, butyl, pentyl and hexyl) and higher alkyl (e. g., heptyl, octyl, nonyl, decyl, undecyl, dodecyl, heptadecyl and octadecyl); alkenyl, such as lower alkenyl (e. g., vinyl, allyl, isopropenyl, butenyl, pentenyl and hexenyl) and higher alkenyl (e. g., heptenyl, octenyl, decenyl, undecnyl and heptadecenyl); alkadienyl (e. g., pentadienyl and heptadecyldienyl); alkatrienyl (e. g., heptadecatrienyl); alkynyl (e. g., ethnyl, propynyl, octynyl and undecynyl); alkenynyl (e. g. butenynyl); and alkadienynyl.

These compounds are prepared by the process of this invention which essentially comprises interacting a l-hydroxy-Z-pyridinethione of the formula wherein R and n are as hereinbefore defined, with either a fatty acid halide (e. g., R-COX) or a fatty acid anhydride [e. g., (RCO)2O]. For the preparation of a mixed anhydride of a lower fatty acid, either process is utilizable. For the preparation of a mixed anhydride of a higher fatty acid, however, the preferred method is that of the interaction of the pyridinethione with an acyl halide (preferably an acyl chloride). This reaction is most advantageously conductedin a basic medium (e. g., an organic base such as pyridine, or an aqueous inorganic base such as aqueous sodium hydroxide).

Suitable pyridinethiones, utilizable as starting materials in the process of this invention, are disclosed in U. S. Patent of Shaw et al., No. 2,686,786, granted August 17, 1954, and U. S. application of Bernstein et al., Serial No. 548,545, filed November 22, 1955, and include: l-hydroxy-Z-pyridinethione; l-hydroxy-x-(lower alkoxy)-2- pyridinethiones (e. g., 1-hydroxy-3-ethoxy-2-pyridinethione); l-hydroxy-x-(halo) -2-pyridinethiones (e. g., lhydroxy-5-bromo-2-pyridinethione); l-hydroxy-x-(lower alkyl)-2-pyridinethiones (e. g., 1-hydroxy-3-methyl-2- pyridinethione, 1-hydroxy-4-methyl-2-pyridinethione, 1- hydroxy 5 methyl 2 pyridinethione and 1-hydroxy-6- methyl-2-pyridinethione); and l-hydroxy-x,x-di(lower alkyl)-2-pyridinethiones (e. g., l-hydroxy-4,6-dimethyl-2- pyridinethione) Suitable fatty acids whose anhydrides or acyl halides 2,758,116 Patented Aug. 7, 1956 are utilizable as starting materials in the process of this invention include: saturated fatty acids, such as lower fatty acids (e. g., acetic, propionic, butyn'c, valeric, caproic and enanthic acid) and higher fatty acids (e. g., caprylic, capric, undecylic, lauric, myristic, palmitic, stearic and nondecylic acid); and unsaturated fatty acids, such as alkcnoic acids (e. g., acrylic, crotonic, pentenic, hexenic, undecenoic, and oleic acids), alkadienoic acids (e. g., sorbic and linoleic acids), alkatrienoic acids (e. g., linolenic acid), alkynoic acids (e. g., propynoic, butynoic, penynoic, palmitolic and stearolic acids), alkenynoic acids and .alkadienynoic acids.

The following examples are illustrative of, but not limitative of, the invention [all temperatures being in centigrade]:

EXAMPLE 1 Anhydride of 1-hydr0xy-2-pyridinethione and acetic acid EXAMPLE 2 To a solution of 25.4 g. (0.2 M) of l-hydroxy-Z- pyridinethione in 300 cc. of dry pyridine is added 15.7 g. (0.2 M) of acetyl chloride at 20-25". A yellow precipitate forms immediately. After complete addition the reaction is heated at 90 for two hours and then cooled. The solid which precipitates is filtered off and the filtrate concentrated to about 100 cc. under reduced pressure and then poured into 700 g. of cracked ice and Water. The tan crystalline solid is filtered and dried to yield about 12 g. of product melting at -86. After recrystallization from 400 cc. of hexane cc. of ethyl acetate, the product weights about 8.5 g. and melts at about 87-88. There is no depression with sample prepared by treating 1-hydroxy-2-pyridinethione with acetic anhydride (Example 1).

cedure of Example 2, the anhydride 0f lfh d pyridinethione and propionic acid is produced.

Furthermore, when l-hydroxy 5 bromo-Z-pyridinethione or 1-hydroxy-5-methyl-2-pyridinethione is substituted for 1-hydroxy-2-pyridinethione in the procedure of Example 1 or 2, the anhydride of acetic acid and l-hydroxy-S-bromo-2-pyridinethione and l-hydroxy-S-methyl- Z-pyridinethione are formed, respectively.

EXAMPLE 3 Anhydride of 1-hydr0xy-2-pyridinethi0ne and stearic acid 25.4 g. (0.2 M) of 1-hydroxy-Z-pyridinethione is dissolved in 300 cc. of cold dry pyridine and 60.4 g. (0.2 M) of stearoyl chloride (B. P. 144l46/2) is added at 20-25. A crystalline precipitate forms immediately. After complete addition the reaction is heated at 80-90 for 4 hours, whereupon a clear solution forms. After standing overnight the crystalline solid which precipitates is filtered off. Weight about 18 g. (theory for pyridine HC1=21 g.). The filtrate is concentrated to about 100 cc. under reduced pressure and then poured into 1500 cc. water. A yellow solid crystallizes. This is filtered off and dissolved in 1 liter of ether. The ether is washed with 2 x 300 cc. H20 and then dried over MgSO4. The ether is removed and the solid residue weighs about SEARCH ROOM 3 59 g. (75%); M. P. about 5153. After recrystallization from 500 cc. hexane, the compound weighs about 31 g. (40%) and melts at about 5153.

Similarly, other higher fatty acid chlorides, such as lauroyl chloride and myristoyl chloride, can be reacted with 1-hydroxy-2-pyridinethione to yield the respective lauric acid and myristic acid anhydrides.

EXAMPLE 4 Anhydride of 1-hydr0xy-2-pyridinethi0ne and lo-undecenoic acid To a solution of 25.4 g. (0.2 M) of 1-hydroxy-2- pyridinethione in 250 cc. of dry pyridine is added 40.4 g. (0.2 M) of undecylenyl chloride at 20. After complete addition the mixture is heated at 8090 for 3 hours and then cooled. The solid which precipitates out is filtered off and the filtrate is concentrated to about 100 cc. under reduced pressure. The residue is poured into 1 liter of water and a red-brown oil precipitates. The oil is extracted with 2 x 500 cc. ether and the ether washed with 2 x 100 cc. 5% sodium hydroxide. The ether is dried over MgSO4 and then removed. The residue is distilled to give about 4 g. of anhydride boiling at 155-158/2.5 mm.

EXAMPLE 5 To a solution of 3.17 g. (0.025 M) of 1-hydroxy-2- pyridinethione in 30 cc. of 1 N NaOH is added 5 g. (0.025 M) of undecylenyl chloride. The mixture is shaken for 2 /2 hours, and then the oil remaining is extracted with 75 cc. of ether. The ether is washed with 50 cc. of water and then dried over MgSO4. The ether is removed and the residue distilled to give about 2 g. of anhydride boiling at 153155/2 mm.

EXAMPLE 6 Anhydride of 1-hydr0xy-2-pyridinethione and sorbic acid To a solution of 25.4 g. (0.2 M) of 1-hydroxy-2- pyridinethione in 250 cc. of dry pyridine is added 26.1 g. (0.2 M) of sorboyl chloride at 25. After complete addition the solution is heated at 8090 for three hours and then cooled. The solid which precipitates is filtered off, and the filtrate is concentrated to about 100 cc. under reduced pressure. The residue is diluted with 1200 cc. of water, and a dark oily precipitate forms. This granulates upon trituration with water to give about 23 g. red-brown solid, M. P. approximately 82-84". After two recrystallizations from hexane-alcohol (11), the compound Weighs about 8 g. and melts at about 93-94".

The anhydrides of this invention are active bactericides and fungicides, as evidenced by the in vitro spectra tabulated in the following table, wherein the effectiveness of the anhydrides of l-hydroxy-Z-pyridinethione with acetic acid (A) and stearic acid (B) is determined:

Minimum Inhibiting Concentration (MIC) 111 micrograms per ml. Microorganism g/m1.)

Compound Compound A B Bacteria:

Staphlococcus 209P 0.08 0. 8 K'lebsiella pneumom'ce 2 25 Bacillus of Calmette and Gucnin 0.01 0. 03 Fungi:

Aspcrgt'llus fumtgatus 1. 5 13. 0 Aspergillus niger"... 0. 3 Microsporum cam's 0.3 Candida albicans 0. 8 13.0 lllicrosporum audouini 10. 4 1.6 Penicilliu'm notatum 0. 4 25. 0 Rhodoiorula glutim's 0.3 Saccharomgces cerevisiae 0. 4 6.0 Trish ophyton mentagrophytes 0. 4 6.0 Fusarz'um bulbigenum 0. 4 6. O Ceratostomella ulmi 0.3 3. O Botrytis cinerea 3.0

The anhydrides of this invention can, therefore, be used as preservatives (for example, in leather, paper and fabrics) and especially in paints and varnishes [wherein the mixed anhydrides of higher fatty acids are particu larly well adapted since, unlike l-hydroxy-2-pyridinethione and the alkali metal salts thereof, they are oilsoluble] to render them proof against mildew or other fungus attack. In the protection of paints, for example, the mixed anhydrides are simply mixed with the paint.

The mixed nh esof this invention find further use des, the mixed anhydride being added eitli''r directly tothe soil (by sprinkling the mixed anhydride itself or a comgosi tion of the mixed anhydride and suitable diluents onto the surface of the soil and then thoroughly intermixing the soil and mixed anhydride) or directly to plant foliage by spraying a composition thereof with a suitable carrier.

The invention may be otherwise variously embodied within the scope of the appended claims.

We claim:

1. A mixed anhydride of a l-hydroxy-2-pyridinethione and a fatty acid.

2. A compound of the general formula wherein RC0 is the acyl radical of a fatty acid, R is selected from the group consisting of hydrogen, lower alkyl, lower alkoxy and halogen, and n is a positive integer no higher than four.

3. A mixed anhydride and a fatty acid.

4. A mixed anhydride and acetic acid.

5. A mixed anhydride and stearic acid.

6. A mixed anhydride and IO-undecenoic acid.

7. A mixed anhydride and sorbic acid.

8. A process for preparing a mixed anhydride of a 1-hydroxy-2-pyridinethione and a fatty acid, which comprises interacting the 1-hydroxy-2-pyridinethione and a compound selected from the group consisting of a fatty acid halide and a fatty acid anhydride, and recovering the resultant mixed anhydride.

9. The process of claim 8, wherein the 1-hydroxy-2- pyridinethione is unsubstituted l-hydroxy-2-pyridinethione.

of l-hydroxy-2-pyridincthionc of l-hydroxy-2-pyridinethione of l-hydroxy-2-pyridinethione of 1-hydroxy-2-pyridinethione of l-hydroxy-Z-pyridinethionc References Cited in the file of this patent UNITED STATES PATENTS 2,686,786 Shaw et al. Aug. 17, 1954 

1. A MIXED ANHYDRIDE OF A 1-HYDROXY-2-PYRIDINETHIONE AND A FATTY ACID. 